Introduction
Antigens are substances that can induce an immune response, for example, a "humoral response" or B-cell lymphocyte response that results in antibody production. Another typical response is the stimulation of T-cells, viz., a "cellular response." (T-cells are another type of lymphocyte that have undergone differentiation in the thymus gland.) T-cells are capable of destroying abnormal cells such as those infected by certain types of viruses or other pathogens. T-cells also are involved in antibody production by B-cells. Accordingly, an antigen can react either with antibodies or with receptors on the T-cells that it stimulates. Antibodies and T-cell receptors are specific for the inducing antigen.
Antibodies and T-cell receptor molecules possess variable regions that are responsible for specific antigenic recognition. The region of the antigen that actually binds to the antibody or T-cell receptor is termed the antigenic determinant or "epitope." Similarly, the variable regions of antibodies and T-cell receptors also contain determinants, or "idiotypes" that are immunogenic and are capable of initiating an anti-antibody antibody response, i.e., an anti-idiotype ("anti-id") immune response.
More particularly, idiotopes are associated with the variable regions of antibody and T-cell receptors. These variable regions confer antibody and T-cell receptor specificity for antigens. Idiotypes are immune system markers on antibodies and T-cell receptors. An idiotype is immunologically defined by reactivity with more than one anti-idiotypic antibody that recognizes an idiotypic determinant or idiotope within a given idiotype; i.e., an idiotype is made up of a collection of idiotopes. Idiotopes are best defined by their binding to monoclonal anti-idiotypic antibodies. It also should be noted that idiotopes are distinct from isotypic (immunoglobulin class-specific), xenotypic (species specific) and allotypic (certain population sub-group specific) determinants.
Each antibody and T-cell receptor has at least one paratope that is the binding site for an antigen determinant (the epitope). A paratope may serve as an idiotope, i.e., the paratope may stimulate an anti-idiotypic response in which, like the original antigen, an anti-anti-idiotopic antibody bind to an epitope within the paratope. A subset of anti-paratope anti-idiotype ("anti-id") antibodies may mimic the immunologic properties of the original antigen and are known as "Ab2 betas" or "internal images" antibodies. In addition to the anti-paratopic anti-ids that mimic the original antigen, other anti-id antibodies define antibody and T-cell receptor idiotopes that also participate in the regulation of immune responses. These idiotypes are termed regulatory idiotypes and they are not necessarily "internal images" of the original antigen. For a general discussion of these background principles, see Burdette, S. and Schwartz, R., New Eng. J. of Med. 317:219 (1987).